Scientists synthesize compound to flush HIV out of hiding

Washington, May 2 : Stanford chemists have come up with a way to chemically produce two compounds that occur naturally in plants that can activate and bring out dormant HIV from its host's T cells, thereby making the virus susceptible to attacks by antiretroviral medicines.

HIV often retreats inside the host's T cells to escape the effects of antiretroviral "cocktails", and lies there in dormant form for decades, waiting for an opportunity to burst forth in a fresh round of infection.

Stanford chemist Paul Wender says that the virus may be flushed out in the open to make it the target of the immune system and antiretroviral therapies with the help of synthetic prostratin, found in the Mamala plant (Homalanthus nutans) that grows in the Samoan rainforest, and DPP, a molecular relative of prostratin found in resin spurge (Euphorbia resinifera) that grows in arid regions.

"We're not sure how far this will go, but certainly, from a theoretical point of view, it has promise of taking therapy to the next level-that is, addressing issues related to eradication of the disease, of the virus, at least," said Wender, the Francis W. Bergstrom Professor.

In a study paper published in the journal Science, the researcher revealed that both compounds had shown some promise to act as activators of dormant HIV in previous studies.

He said that the research was, however, hampered because the two compounds were difficult to obtain, particularly in the quantities needed for practical lab work on their mode of action and therapeutic potential.

Fear of ecological damage prevented scientists from contemplating heavily harvesting the wild plants that provide the two compounds, he added.

But now, with the new technique developed by his team, said Wender, synthetic prostratin and DPP could be readily made in the lab.

"We have now minimized, if not eliminated, the issue of availability of prostratin and DPP. But equally, if not more importantly, we have opened access to other compounds that might be similar in structure but superior in function," he said.

He said that synthetic prostratin and DPP could enable scientists to take the basic compounds, and tinker with the structure and related function.

"We could find out how to improve them by reverse engineering: figuring out what is important and what isn't important," Wender said.

"We could begin to design and synthesize molecules that would never be found in nature but might actually be therapeutically more beneficial than what has been found thus far," he added.